A Pfizer gene therapy for the rare muscle-wasting disease Duchenne muscular dystrophy did not help patients’ ability to walk or stand up in a pivotal clinical trial. The pharmaceutical giant is still weighing its next steps for the therapy, but analysts say these disappointing trial results, the latest in a series of setbacks, likely mark the end for this program.
The Phase 3 test enrolled boys ages 4 to 7 who still had the ability to walk. The trial’s main goal was to show an improvement in motor function compared to a placebo. Without providing specific figures, Pfizer said after Wednesday’s market close that its gene therapy did not achieve this goal measured one year after treatment. Secondary goals include measuring how fast patients can run or walk for 10 meters and how quickly they can rise from the floor. On these measures, there was no significant difference between the gene therapy arm and the placebo group.
“We are extremely disappointed that these results did not demonstrate the relative improvement in motor function that we had hoped,” Dan Levy, Pfizer’s development head for Duchenne muscular dystrophy, said in a prepared statement. “We plan to share more detailed results from the study at upcoming medical and patient advocacy meetings, with the goal of ensuring that learnings from this trial can help improve future clinical research and development of treatment options that can improve care for boys living with Duchenne muscular dystrophy.”
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Duchenne is an inherited disorder that results in the inability to produce normal versions of dystrophin, a protein key to muscle function. Patients develop progressively worsening muscle weakness that robs them of their ability to walk. The muscle weakness eventually affects the lungs and the heart, becoming fatal.
[Paragraph updated to correct the study on dosing pause.] The Pfizer gene therapy, fordadistrogene movaparvovec, uses an engineered virus to deliver to muscle cells a mini-version of the gene that codes for dystrophin. Its clinical development path has had prior setbacks. A patient death in 2021 led to a clinical hold on tests of the therapy. Pfizer was later cleared to resume clinical trials after implementing additional safety measures. But last month, Pfizer disclosed a patient death in a Phase 2 study evaluating its Duchenne gene therapy in boys ages 2 to 3. Dosing in that study is complete. Pfizer said dosing in the crossover arm of the Phase 3 study has paused as the company continues to gather information to understand what caused the patient death in the Phase 2 test. In the latest results reported Wednesday, Pfizer said the gene therapy’s safety profile was manageable and adverse effects were mostly mild to moderate.
The developments unfolding for Pfizer’s gene therapy come as the FDA weighs whether to award full approval to Elevidys, a Duchenne gene therapy developed by Sarepta Therapeutics. Nearly a year ago, the Sarepta therapy won accelerated approval for Duchenne patients ages 4 and 5. But last fall, the company reported the failure of the Phase 3 study meant to confirm the therapy’s benefit and support expansion to a wider range of patients. That pivotal study evaluated patients with the same measures used for Pfizer’s pivotal study.
Leerink Partners analyst Joseph Schwartz draws distinctions between the two gene therapy programs. Though both failed in Phase 3, Sarepta’s therapy showed statistically significant improvement according to its trial’s secondary measures, which are more sensitive in detecting benefit, he said in a Thursday research note. Furthermore, Sarepta’s gene therapy does not have the safety questions overhanging the Pfizer gene therapy.
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“Thus, with no efficacy signals and a less-than-pristine safety profile, we see this readout as the final nail in the coffin for the program and think it is unlikely to move forward,” Schwartz said.
William Blair analyst Tim Lugo said in a research note that his firm did not view Pfizer’s gene therapy as a real competitive threat to Sarepta due to the safety concerns throughout its development. He echoed Schwartz’s comments about the Sarepta therapy’s ability to hit the secondary goals of its study.
“We believe overall the totality of the data generated to date support the efficacy of Elevidys, the current 4- and 5-year-old label, a conversion to full approval, and a broader expansion to include older boys and into non-ambulatory patients,” Lugo said. “However, we believe expansion into non-ambulatory patients is more of a stretch, and we would not be surprised if these patients are excluded from the expanded label.”
Sarepta’s Elevidys faces a June 21 target date for an FDA decision.
Photo: Dominick Reuter/AFP, via Getty Images
